Harlan Cytotest Cell Research Harlan CCR GmbH

Roßdorf, Germany

Harlan Cytotest Cell Research Harlan CCR GmbH

Roßdorf, Germany
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Bohnenberger S.,Harlan Cytotest Cell Research Harlan CCR GmbH | Bruce S.W.,BioReliance | Kunkelmann T.,Harlan Cytotest Cell Research Harlan CCR GmbH | Pant K.,BioReliance | And 4 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

This catalogue is a display of Syrian hamster embryo (SHE) cell colony photos representative of the cell transformation assay (CTA) carried out at pH 6.7. It is intended as a visual aid for the identification and the scoring of cell colonies in the conduct of the assay.A proper training from experienced personnel together with the protocol reported in this issue and the present photo catalogue will support method transfer and consistency in the assay results. © 2011 Elsevier B.V.


Maire M.-A.,French National Center for Scientific Research | Pant K.,BioReliance | Poth A.,Harlan Cytotest Cell Research GmbH Harlan CCR | Schwind K.-R.,BASF | And 8 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

The European Centre for the Validation of Alternative Methods (ECVAM) has organised an interlaboratory prevalidation study on the Syrian hamster embryo (SHE) cell transformation assay (CTA) at pH 7.0 for the detection of rodent carcinogens. The SHE CTA at pH 7.0 has been evaluated for its within-laboratory reproducibility, transferability and between-laboratory reproducibility. Four laboratories using the same basic protocol with minor modifications participated in this study and tested a series of six coded-chemicals: four rodent carcinogens (benzo(a)pyrene, 3-methylcholanthrene, 2,4-diaminotoluene and o-toluidine HCl) and two non-carcinogens (anthracene and phthalic anhydride). All the laboratories found the expected results with coded chemicals except for phthalic anhydride which resulted in a different call in only one laboratory. Based on the outcome of this study, it can be concluded that a standardised protocol is available that should be the basis for future use. This protocol and the assay system itself are transferable between laboratories and the SHE CTA at pH 7.0 is reproducible within- and between-laboratories. © 2011 Elsevier B.V.


Maire M.-A.,French National Center for Scientific Research | Pant K.,BioReliance | Phrakonkham P.,European Commission - Joint Research Center Ispra | Poth A.,Harlan Cytotest Cell Research GmbH Harlan CCR | And 8 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

The Syrian hamster embryo (SHE) cell transformation assay (CTA) is a short-term in vitro assay recommended as an alternative method for testing the carcinogenic potential of chemicals. SHE cells are " normal" cells since they are diploid, genetically stable, non-tumourigenic, and have metabolic capabilities for the activation of some classes of carcinogens. The CTA, first developed in the 1960s by Berwald and Sachs (1963,1964) [3,4], is based on the change of the phenotypic feature of cell colonies expressing the first steps of the conversion of normal to neoplastic-like cells with oncogenic properties. Pienta et al. (1977) [22] developed a protocol using cryopreserved cells to enhance practicality of the assay and limit sources of variability. Several variants of the assay are currently in use, which mainly differ by the pH at which the assay is performed. We present here the common version of the SHE pH 6.7 CTA and SHE pH 7.0 CTA protocols used in the ECVAM (European Centre for the Validation of Alternative Methods) prevalidation study on CTA reported in this issue. It is recommended that this protocol, in combination with the photo catalogues presented in this issue, should be used in the future and serve as a basis for the development of the OECD test guideline. © 2011 Elsevier B.V.


Sasaki K.,Hatano Research Institute | Bohnenberger S.,Harlan Cytotest Cell Research GmbH Harlan CCR | Hayashi K.,Hatano Research Institute | Kunkelmann T.,Harlan Cytotest Cell Research GmbH Harlan CCR | And 8 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

The present protocol has been developed for the BALB/c 3T3 cell transformation assay (CTA), following the prevalidation study coordinated by the European Centre for the Validation of Alternative Methods (ECVAM) and reported in this issue (Tanaka et al. [16]). Based upon the experience gained from this effort and as suggested by the Validation Management Team (VMT), some acceptance and assessment criteria have been refined compared to those used during the prevalidation study. The present protocol thus describes cell culture maintenance, the dose-range finding (DRF) experiment and the transformation assay, including cytotoxicity and morphological transformation evaluation. Use of this protocol and of the associated photo catalogue included in this issue (Sasaki et al. [17]) is recommended for the future conduct of the BALB/c 3T3 CTA. © 2012 Elsevier B.V.


Sasaki K.,Hatano Research Institute | Bohnenberger S.,Harlan Cytotest Cell Research Harlan CCR GmbH | Hayashi K.,Hatano Research Institute | Kunkelmann T.,Harlan Cytotest Cell Research Harlan CCR GmbH | And 7 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

This catalogue is a display of focus photos representative of the BALB/c 3T3 cell transformation assay (CTA). It is intended as a visual aid for the identification and the scoring of foci in the conduct of the assay.A proper training from experienced personnel together with the protocol reported in this issue and the present photo catalogue will support method transfer and consistency in the assay results. © 2012 Elsevier B.V.


Tanaka N.,Hatano Research Institute | Bohnenberger S.,Harlan Cytotest Cell Research GmbH Harlan CCR | Kunkelmann T.,Harlan Cytotest Cell Research GmbH Harlan CCR | Munaro B.,European Commission - Joint Research Center Ispra | And 8 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

The cell transformation assays (CTAs) have attracted attention within the field of alternative methods due to their potential to reduce the number of animal experiments in the field of carcinogenicity. The CTA using BALB/c 3T3 cells has proved to be able to respond to chemical carcinogens by inducing morphologically transformed foci. Although a considerable amount of data on the performance of the assay has been collected, a formal evaluation focusing particularly on reproducibility, and a standardised protocol were considered important. Therefore the European Centre for the Validation of Alternative Methods (ECVAM) decided to coordinate a prevalidation study of the BALB/c 3T3 CTA. Three different laboratories from Japan and Europe participated. In the study the following modules were assessed stepwise: test definition (Module 1) consisted of the standardisation of the protocol, the selection of the cell lineage, and the preparation of a photo catalogue on the transformed foci. The within-laboratory reproducibility (Module 2) and the transferability (Module 3) were assessed using non-coded and coded 3-methylcholanthrene. Then, five coded chemicals were tested for the assessment of between-laboratory reproducibility (Module 4). All three laboratories obtained positive results with benzo[a]pyrene, phenanthrene and o-toluidine HCl. 2-Acetylaminofluorene was positive in two laboratories and equivocal in one laboratory. Anthracene was negative in all three laboratories. The chemicals except phenanthrene, which is classified by IARC (http://monographs.iarc.fr) as group 3 " not classifiable as to its carcinogenicity to human" , were correctly predicted as carcinogens. Further studies on phenanthrene will clarify this discrepancy. Thus, although only a few chemicals were tested, it can be seen that the predictive capacity of the BALB/c 3T3 CTA is satisfactory.On the basis of the outcome of this study, an improved protocol, incorporating some changes related to data interpretation, has been developed. It is recommended that this protocol be used in the future to provide more data that may confirm the robustness of this protocol and the performance of the assay itself. During the study it became clear that selecting the most appropriate concentrations for the transformation assay is crucial. © 2012 Elsevier B.V.


Pant K.,BioReliance | Bruce S.W.,BioReliance | Sly J.E.,BioReliance | Kunkelmann T.,Harlan Cytotest Cell Research GmbH Harlan CCR | And 5 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2012

The Syrian hamster embryo (SHE) cell transformation assay (CTA) is an important in vitro method that is highly predictive of rodent carcinogenicity. It is a key method for reducing animal usage for carcinogenicity prediction. The SHE assay has been used for many years primarily to investigate and identify potential rodent carcinogens thereby reducing the number of 2-year bioassays performed in rodents. As for other assays with a long history of use, the SHE CTA has not undergone formal validation. To address this, the European Centre for the Validation of Alternative Methods (ECVAM) coordinated a prevalidation study. The aim of this study was to evaluate the within-laboratory reproducibility, test method transferability, and between-laboratory reproducibility and to develop a standardised state-of-the-art protocol for the SHE CTA at pH 6.7. Formal ECVAM principles for criteria on reproducibility (including the within-laboratory reproducibility, the transferability and the between-laboratories reproducibility) were applied. In addition to the assessment of reproducibility, this study helped define a standard protocol for use in developing an Organisation for Economic Co-operation and Development (OECD) test guideline for the SHE CTA. Six compounds were evaluated in this study: benzo(a)pyrene, 3-methylcholanthrene, o-toluidine HCl, 2,4-diaminotoluene, phthalic anhydride and anthracene. Results of this study demonstrate that a protocol is available that is transferable between laboratories, and that the SHE CTA at pH 6.7 is reproducible within- and between-laboratories. © 2011 Elsevier B.V.


Aunon-Calles D.,Seprox Biotech | Giordano E.,IMDEA Madrid Institute for Advanced Studies | Bohnenberger S.,Harlan Cytotest Cell Research GmbH Harlan CCR | Visioli F.,IMDEA Madrid Institute for Advanced Studies
Pharmacological Research | Year: 2013

Hydroxytyrosol (HT) is an olive-derived phenol endowed with several biological activities, some of which demonstrated in humans. Indeed, the European Food Safety Authority (EFSA) allows the health claim that HT (≥5 mg/d) "protects LDL particles from oxidative damage". In terms of safety, HT has been investigated as the predominant part of raw olive mill waste water extracts that have been granted the Generally Recognized as Safe (GRAS) status. Also, a long-term toxicological study of HT proposed a NOAEL of 500 mg/kg/d. As several HT-containing supplements and functional foods are entering the market, we sought to investigate the genotoxic and mutagenic potential of HT, using well-established in vitro models, i.e. the chromosomal aberration assay and the Ames test (by using the Salmonella typhimurium TA 100, TA98, TA1535, and TA1537 strains and Escherichia coli WP2(pKM101)), with and without S9-induced metabolic activation). Even though we cannot rule out that prolonged exposure to HT and its metabolites might have untoward effects, the results of this study indicate that HT is non-genotoxic and non-mutagenic at concentrations that far exceed those attainable after intake. © 2013 Elsevier Ltd. All rights reserved.

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